Beta(β)-glucan is a complex carbohydrate, generally derived from several sources, including yeast, bacteria, fungi and cereal grains. Each type of β-glucan has a unique structure in which glucose is linked together in different ways, resulting in different physical and chemical properties. For example, β(1,3) glucan derived from bacterial and algae is linear, making it useful as a food thickener. The frequency of side chains, known as the degree of substitution or branching frequency, regulated secondary structure and solubility. Beta glucan derived from Yeast is branched with β(1,3) and β(1,6) linkages, enhancing its ability to bind to and stimulate macrophages. β(1,3/1,6) glucan purified from baker's yeast (Saccharomyces cerevisiae) is a potent anti-infective beta-glucan immunomodulator.
The cell wall of S. cerevisiae is mainly composed of β-glucans, which are responsible for its shape and mechanical strength. While best known for its use as a food grade organism, yeast is also used as a source of zymosan, a crude insoluble extract used to stimulate a non-specific immune response. Yeast-derived beta(1,3) glucans stimulate the immune system, in part, by activating the innate anti-fungal immune mechanisms to fight a variety of targets. Baker's yeast β(1,3/1,6) glucan is a polysaccharide composed entirely of β(1,3)-linked sugar (glucose) molecules forming the polysaccharide backbone with periodic β(1,3) branches linked via β(1,6) linkages). It is more formally known as poly-(1,6)-β-D-glucopyranosyl-(1,3)-β-D-glucopyranose. Glucans are structurally and functionally different depending on the source and isolation methods.
Beta glucans possess a diverse range of activities. The ability of β-glucan to increase nonspecific immunity and resistance to infection is similar to that of endotoxin. Early studies on the effects of β(1,3) glucan on the immune system focused on mice. Subsequent studies demonstrated that β(1,3) glucan has strong immunostimulating activity in a wide variety of other species, including earthworms, shrimp, fish, chicken, rats, rabbits, guinea pigs, sheep, pigs cattle and humans. Based on these studies, β(1,3) glucan represents a type of immunostimulant that is active across the evolutionary spectrum, likely representing an evolutionarily innate immune response directed against fungal pathogens. However, despite extensive investigation, no consensus has been achieved on the source, size, and form of β(1,3) glucan ideal for use as an immunostimulant.
Radiation and chemotherapeutic drugs can suppress the production of blood cells and platelets in the bone marrow, an adverse side-effect known as myelosuppression. Exposure to radiation can cause a rapid depletion of immune (hematopoietic) cells and platelets derived from the bone marrow (BM) that are necessary for controlling life threatening infections and bleeding episodes.
Radioprotectants allow for more effective antitumor treatments by minimizing the side effects of radiotherapy or chemotherapy. Advances in radioprotection also enable military forces to operate, when required, in nuclear or radioactive combat environments while minimizing both long-term and short-term risks of the consequences of exposure to ionizing radiation. Radioprotectants can also be useful for protecting or treating astronauts who are exposed to space radiation. Finally, readily available and easily administered radioprotectants could be of crucial importance in minimizing the damage from terrorist actions or industrial nuclear accidents.
The use of β(1,3/1,6) glucans as hematopoietic agents has been tentatively explored in several references. For example, U.S. Pat. No. 5,532,223 by Jamas et al. demonstrates the use of parenteral neutral soluble glucan to stimulate hematopoietic and immunological effects without stimulating the production of undesired cytokines. Patchen and colleagues demonstrated that parenterally administered soluble and particulate beta-glucans can enhance hematopoietic recovery and the ability to resist infection in mice exposed to radiation when administered either before or after exposure to radiation. See M. L. Patchen et al., “Glucan: mechanisms involved in its ‘radioprotective’ effect”, J. Leukoc. Biol., 42, 95 (1987). Beta glucan has also been used as a topical antioxidant to protect the skin from damage caused by ultraviolet radiation. See J. A. Greene, “Composition for protecting skin from damaging effects of ultraviolet light”, U.S. Pat. No. 6,235,272. However, these laboratory studies have not provided a convenient formulation of β-glucan. The majority of these applications utilize soluble material that requires administration by injection, a costly and painful route that can result in poor patient compliance. However, many drugs are not amenable to oral formulation due to properties that limit oral bioavailability. Therefore, a need exists for formulations that can lead to greater patient compliance and maintain bioavailability. Additionally, there remains a need for a formulation of β-glucan, particularly an oral formulation, which can be readily stored and administered to humans to prevent or treat myelosuppression and serve as an effective radioprotectant.